E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary insomnia in adults with low endegenous melatonin. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
EU Version To assess the sustained long-term efficacy of Circadin 2 mg vs placebo for up to six months of treatment as assessed by changes from baseline in subjective sleep quality (as measured by the mean PSQI global score) during visits 6 and 7 (mean value) in all patients aged 55-80.
US Version Following three weeks treatment with Circadin® 2 mg or placebo, to compare the change from baseline in subjective sleep latency (as measured by the sleep diary, question 3) in “low excretors”. |
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E.2.2 | Secondary objectives of the trial |
EU Version In all patients aged 55-80 to compare: -change from baseline in mean subjective sleep latency (as measured by question 2 of the PSQI at visits 6, 7). -change from baseline in quality of life (as measured by the WHO-5 scale at visits 6, 7). -Clinical Global Impressions (CGI) global improvement at visits 6 and 7. -To assess withdrawal effect after discontinuation (as measured by the Tyrer scale) of Circadin vs placebo following 6 months of treatment.
US Version Following three weeks treatment with Circadin® 2 mg or placebo, to compare: -change from baseline in subjective sleep latency (Sleep Diary, question 3) patients aged 65-80 inclusive. -change from baseline in “low excretors” compared to “high excretors” on efficacy variables in different age bands -the rate of responders in patients aged 55 to 80 -To assess safety parameters in the total population following three weeks treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• male or female and aged 18-80 years • willing to take a 6-SMT level evaluation test • suffering from primary insomnia according to DSM-IV criteria (307.42 primary insomnia, Appendix 24.3) (Based on a Sleep History Questionnaire that is given to the patient before Visit 1, Appendix 24.9) • sleep latency of at least 20 minutes • have not been using BZD and non-BZD hypnotics for the past 2 weeks or more • have not been using psychotropic treatments for the past 3 months or more • are stabilized on non-psychotropic treatments for more than 1 month • are willing to sign a written informed consent to participate in the study
Patients completing the two week placebo baseline/screening who continue to meet the entry criteria and who fulfill the following will be eligible to be randomisedrandomized if:
• Negative drug screen (BZD or opiates). Where the patient has reported use of opiate analgesics for pain relief (not hypnosis) at visit 1 the opiate screen may be positive and the patient still randomised. • No reported use of BZD and non-BZD hypnotics, antihistamines or psychotropic treatments during the two-week placebo baseline/screening period • A good compliance during the two-week placebo baseline/screening period defined as 70% to 130% of prescribed tablets • Correct use of the Diary and Leeds SEQ
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E.4 | Principal exclusion criteria |
• Use of benzodiazepines or other hypnotics (including psychotropic treatments) during the study and preceding two weeks. • Alcohol intake more than 30 g of pure alcohol per day and any intake after lunch-time. • Pharmacological immunosuppression • Participation in a clinical trial with any investigational agent within two months prior to study enrollment • According to DSM IV, subjects belonging to the following groups are excluded: 780.59 (breathing related sleep disorder); 307.45 (circadian rhythm sleep disorder); 307.47 (dyssomnia not otherwise specified); 780.xx (sleep disorder due to general medical condition) • Severe neurological, psychiatric disorders especially psychosis, anxiety and depression and alcoholism • Other serious diseases that could interfere with patient assessment • Pregnant or breast feeding women
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E.5 End points |
E.5.1 | Primary end point(s) |
EU Version To assess the sustained long-term efficacy of Circadin 2 mg vs placebo for up to six months of treatment as assessed by changes from baseline in subjective sleep quality (as measured by the mean PSQI global score) during visits 6 and 7 (mean value) in all patients aged 55-80.
US Version Following three weeks treatment with Circadin® 2 mg or placebo, comparison of the change from baseline in subjective sleep latency (as measured by the Sleep Diary, question 3) in “low excretors”. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of last patient |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |